This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To study the effects of chlorhexidine (CHX) and ethylene diamine tetraacetic acid (EDTA) on adhesive properties of moderate fluorosis dentin.Methods:From August to September 2024, a total of 30 freshly extracted, non-carious and non-defective mandibular molars with moderate dental fluorosis, extracted for impaction or orthodontic reasons, were collected from the patients at the Department of Oral and Maxillofacial Surgery at Guiyang Stomatological Hospital and randomly divided into three groups (Groups A, B, and C, n = 10) using a simple randomization method, and pretreated for 60 s with normal saline (Group A), 17%EDTA gel (Group B), and 2%CHX solution (Group C), respectively. Subsequently, microtensile bonding strength testing and microleakage evaluation were performed. Results:The immediate bonding strengths of Groups A, B, and C were (14.23 ± 4.75), (20.94 ± 7.46), and (28.76 ± 14.61) MPa, respectively, and the bonding strengths after aging were (9.89 ± 3.81), (19.05 ± 7.85), and (22.15 ± 8.67) MPa, respectively. There were statistically significant differences in both immediate and aged bonding strengths among the three groups ( F = 6.08, 8.07, P = 0.010, 0.002). The immediate bonding strength of Group C was significantly higher than that of Group A ( P < 0.05), and the post aging bonding strength of both Group B and Group C was significantly higher than that of Group A ( P < 0.05). The proportion of silver staining area with microleakage in Groups A, B, and C were 21.87% (14.65%, 40.15%), 2.34% (1.87%, 5.29%), and 17.54% (4.59%, 20.47%), respectively, with statistically significant differences among the three groups ( H = 27.36, P = 0.001). The proportion of silver stained area with microleakage in Group B was significantly lower than that in Group A and Group C, and the difference was statistically significant ( P < 0.05). Conclusions:Pretreatment of moderate fluorosis dentin with 2%CHX or 17%EDTA can improve resin bongding performance, with EDTA being superior in reducing microleakage and CHX being better in enhancing adhesion strength.

This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.